DAPT regulates Treg/Th17 cells immune balance to inhibit atherosclerosis / 中国免疫学杂志

ABSTRACT

Objective:To observe the effect of Notch signal inhibitor DAPT (γ-secretase inhibitor ) on the pathological changes of atherosclerosis mice and the immune balance of Treg/Th17.Methods:24 ApoE knockout C57BL mice were randomly divided into blank group,model group and DAPT group.The blank group were fed with normal diet ,the model group and the experimental group were fed with high fat diet.After 5 weeks of feeding,the mice in the experimental group were injected with DAPT [100 mg/(kg· d),re-suspended in DMSO],and the other two groups were injected with the equivalent amount of DMSO .After another 5 weeks,pathological changes of the mice in each group were analyzed by HE staining .ELISA was used to detect the level of IL-17 in plasma,and the propor-tion of splenic Treg/Th17 cells in each group was detected by flow cytometry .Results:HE staining results showed that the model group had obvious plaque formation and foam cell formation ,which showed that the AS model was successfully prepared .The degree of arterial disease in the DAPT group was significantly less than that in the model group .The plasma levels of IL-17 in the blank group , model group and DAPT group were(293.94±28.59),(454.05±172.68) and (335.40±89.57) pg/ml,respectively .The percentages of Treg cells in the blank group,model group and DAPT group were(3.80±0.56)%,(2.54±0.38)%and(4.73±0.64)%,respective-ly.The Th17 cell subsets of mice in the blank group , model group and DAPT group were ( 3.46 ±0.23 )%, ( 4.52 ±0.85 )% and (1.38±0.37)%,respectively .Conclusion:DAPT decreased the plasma level of IL-17 in AS mice,inhibited the differentiation of Th17 cell subsets,and promoted the differentiation of Treg ,and reduced the atherosclerosis by changing the Treg/Th17 cells immune balance.